Faculty Bibliography

PURPOSE/OBJECTIVE:Dose-volume data for injury to carotid artery and other major vessels in stereotactic body radiation therapy (SBRT)/SABR head and neck reirradiation were reviewed, modeled, and summarized. METHODS AND MATERIALS/METHODS:A PubMed search of the English-language literature (stereotactic and carotid and radiation) in April 2018 found 238 major vessel maximum point doses in 6 articles that were pooled for logistic modeling. Two subsequent studies with dose-volume major vessel data were modeled separately for comparison. Attempts were made to separate carotid blowout syndrome from other bleeding events (BE) in the analysis, but we acknowledge that all except 1 data set has some element of BE interspersed. RESULTS:Prior radiation therapy (RT) dose was not uniformly reported per patient in the studies included, but a course on the order of conventionally fractionated 70 Gy was considered for the purposes of the analysis (with an approximately ≥6-month estimated interval between prior and subsequent treatment in most cases). Factors likely associated with reduced risk of BE include nonconsecutive daily treatment, lower extent of circumferential tumor involvement around the vessel, and no surgical manipulation before or after SBRT. CONCLUSIONS:Initial data pooling for reirradiation involving the carotid artery resulted in 3 preliminary models compared in this Hypofractionated Treatment Effects in the Clinic (HyTEC) report. More recent experiences with alternating fractionation schedules and additional risk-reduction strategies are also presented. Complications data for the most critical structures such as spinal cord and carotid artery are so limited that they cannot be viewed as strong conclusions of probability of risk, but rather, as a general guideline for consideration. There is a great need for better reporting standards as noted in the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic introductory paper.

PURPOSE/OBJECTIVE:We sought to investigate the tumor control probability (TCP) of spinal metastases treated with stereotactic body radiation therapy (SBRT) in 1 to 5 fractions. METHODS AND MATERIALS/METHODS:PubMed-indexed articles from 1995 to 2018 were eligible for data extraction if they contained SBRT dosimetric details correlated with actuarial 2-year local tumor control rates. Logistic dose-response models of collected data were compared in terms of physical dose and 3-fraction equivalent dose. RESULTS:Data were extracted from 24 articles with 2619 spinal metastases. Physical dose TCP modeling of 2-year local tumor control from the single-fraction data were compared with data from 2 to 5 fractions, resulting in an estimated α/β = 6 Gy, and this was used to pool data. Acknowledging the uncertainty intrinsic to the data extraction and modeling process, the 90% TCP corresponded to 20 Gy in 1 fraction, 28 Gy in 2 fractions, 33 Gy in 3 fractions, and (with extrapolation) 40 Gy in 5 fractions. The estimated TCP for common fractionation schemes was 82% at 18 Gy, 90% for 20 Gy, and 96% for 24 Gy in a single fraction, 82% for 24 Gy in 2 fractions, and 78% for 27 Gy in 3 fractions. CONCLUSIONS:Spinal SBRT with the most common fractionation schemes yields 2-year estimates of local control of 82% to 96%. Given the heterogeneity in the tumor control estimates extracted from the literature, with variability in reporting of dosimetry data and the definition of and statistical methods of reporting tumor control, care should be taken interpreting the resultant model-based estimates. Depending on the clinical intent, the improved TCP with higher dose regimens should be weighed against the potential risks for greater toxicity. We encourage future reports to provide full dosimetric data correlated with tumor local control to allow future efforts of modeling pooled data.

PURPOSE/OBJECTIVE:We sought to investigate the tumor control probability (TCP) of vestibular schwannomas after single-fraction stereotactic radiosurgery (SRS) or hypofractionated SRS over 2 to 5 fractions (fSRS). METHODS AND MATERIALS/METHODS:Studies (PubMed indexed from 1993-2017) were eligible for data extraction if they contained dosimetric details of SRS/fSRS correlated with local tumor control. The rate of tumor control at 5 years (or at 3 years if 5-year data were not available) were collated. Poisson modeling estimated the TCP per equivalent dose in 2 Gy per fraction (EQD2) and in 1, 3, and 5 fractions. RESULTS:Data were extracted from 35 publications containing a total of 5162 patients. TCP modeling was limited by the absence of analyzable data of <11 Gy in a single-fraction, variability in definition of "tumor control," and by lack of significant increase in TCP for doses >12 Gy. Using linear-quadratic-based dose conversion, the 3- to 5-year TCP was estimated at 95% at an EQD2 of 25 Gy, corresponding to 1-, 3-, and 5-fraction doses of 13.8 Gy, 19.2 Gy, and 21.5 Gy, respectively. Single-fraction doses of 10 Gy, 11 Gy, 12 Gy, and 13 Gy predicted a TCP of 85.0%, 88.4%, 91.2%, and 93.5%, respectively. For fSRS, 18 Gy in 3 fractions (EQD2 of 23.0 Gy) and 25 Gy in 5 fractions (EQD2 of 30.2 Gy) corresponded to TCP of 93.6% and 97.2%. Overall, the quality of dosimetric reporting was poor; recommended reporting guidelines are presented. CONCLUSIONS:With current typical SRS doses of 12 Gy in 1 fraction, 18 Gy in 3 fractions, and 25 Gy in 5 fractions, 3- to 5-year TCP exceeds 91%. To improve pooled data analyses to optimize treatment outcomes for patients with vestibular schwannoma, future reports of SRS should include complete dosimetric details with well-defined tumor control and toxicity endpoints.

PURPOSE/OBJECTIVE:As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS). METHODS AND MATERIALS/METHODS:Eligible studies provided NTCPs for the endpoints of radionecrosis, edema, or symptoms after cranial SRS/fSRS and quantitative dose-volume metrics. Studies of patients with only glioma, meningioma, vestibular schwannoma, or brainstem targets were excluded. The data summary and analyses focused on arteriovenous malformations (AVM) and brain metastases. RESULTS:were associated with <10% risk of radionecrosis. CONCLUSIONS:The risk of radionecrosis after SRS and fSRS can be modeled as a function of dose and volume treated. The use of fSRS appears to reduce risks of radionecrosis for larger treatment volumes relative to SRS. More standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses that can refine predictive models of brain toxicity risks.

PURPOSE/OBJECTIVE:Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation. METHODS AND MATERIALS/METHODS:Eligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION). RESULTS:Thirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P = .66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in <1% RION risks include 12 Gy in 1 fraction (which is greater than our recommendation of 10 Gy in 1 fraction), 20 Gy in 3 fractions, and 25 Gy in 5 fractions. Omitting multi-fraction data (and thereby eliminating uncertainties associated with dose conversions), a single-fraction dose of 10 Gy was associated with a 1% RION risk. Insufficient details precluded modeling of NTCP risks after prior radiation therapy. CONCLUSIONS:Optic apparatus NTCP and tolerance doses after single- and multi-fraction stereotactic radiosurgery are presented. Additional standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses and better define RION NTCP after SRS/fSRS.

OBJECTIVE:. compression or gating). METHODS:A PubMed search was performed for identifying literature regarding dose, volume, fractionation, and toxicity (grade 3 or higher) for SBRT treatments for tumors which move with respiration. From the identified papers logistic or probit dose-response models were fitted to the data using the maximum-likelihood technique and confidence intervals were based on the profile-likelihood method in the dose-volume histogram (DVH) Evaluator. RESULTS:Pooled logistic and probit models for grade 3 or higher toxicity for aorta, chest wall, duodenum, and small bowel suggest a significant difference when live motion tracking was used for targeting tumors with move with respiration which was on the average 10 times lower, in the high dose range. CONCLUSION/CONCLUSIONS:Live respiratory motion management appears to have a better toxicity outcome when treating targets which move with respiration with very steep peripheral dose gradients. This analysis is however limited by sparsity of rigorous data due to poor reporting in the literature.

PURPOSE/OBJECTIVE:The purpose of this study is to quantify dosimetric changes throughout the delivery of oropharyngeal cancer treatment and to investigate the application of statistical process control (SPC) for the management of significant deviations during the course of radiotherapy. METHODS:Thirteen oropharyngeal cancer patients with daily cone beam computed tomography (CBCT) were retrospectively reviewed. Cone beam computed tomography images of every other fraction were imported to the Velocity software and registered to planning CT using the 6 DOF (degrees of freedom) couch shifts generated during patient setup. Using Velocity "Adaptive Monitoring" module, the setup-corrected CBCT was matched to planning CT using a deformable registration. Volumes and dose metrics at each fraction were calculated and rated with plan values to evaluate interfractional dosimetric variations using a SPC framework. T-tests between plan and fraction volumes were performed to find statistically insignificant fractions. Average upper and lower process capacity limits (UCL, LCL) of each dose metric were derived from these fractions using conventional SPC guidelines. RESULTS:Gross tumor volume (GTV) and organ at risk (OAR) volumes in the first 13 fractions had no significant changes from the pretreatment planning CT. The GTV and the parotid glands subsequently decreased by 10% at the completion of treatment. There were 3-4% increases in parotid mean doses, but no significant differences in dose metrics of GTV and other OARs. The changes were organ and patient dependent. Control charts for various dose metrics were generated to assess the metrics at each fraction for individual patient. CONCLUSIONS:Daily CBCT could be used to monitor dosimetric variations of targets and OARs resulting from volume changes and tissue deformation in oropharyngeal cancer radiotherapy. Treatment review with the guidance of a SPC tool allows for an objective and consistent clinical decision to apply adaptive radiotherapy.

Purpose: The purpose of this study is to quantify interfractional dosimetric variations in radiotherapy of oropharyngeal cancer and investigate the application of statistical process control (SPC) to determine significantly deviated fractions for management.
Method(s): Thirteen oropharyngeal cancer patients treated by IMRT or VMAT with daily CBCT were retrospectively reviewed. CBCT images of every other fraction were imported to the software Velocity and registered to planning CT using the 6DOF couch shifts generated during patient setup. Using Velocity Adaptive Monitoring module, the setup-corrected CBCT was matched to planning CT using a deformable registration. The module also generated dose volume histograms (DVHs) at each CBCT from planning doses for the deformed plan structure sets. Volumes and dose metrics at each fraction were calculated and rated with plan values to evaluate interfractional dosimetric variations using a SPC framework. T-tests between plan and fraction volumes were performed to find statistically insignificant fractions. Average, upper and lower process capacity limits (UCL, LCL) of each dose metric were derived from these fractions using conventional SPC guidelines.
Result(s): GTV and OAR volumes in first 13 fractions had no significantly changes from the plan, subsequently reduced by 10% to treatment completion, except oral cavity. There were 3%-4% increases in parotid mean doses, but no significant differences in dose metrics of GTVand other OARs. The changes were organ and patient dependent. Control charts for various dose metrics were generated to assess the metrics for individual patient. The occurrences of one or several dose metrics out of the control limits warrant immediate investigation of the fraction.
Conclusion(s): Daily CBCT could be used to monitor dosimetric variations of targets and OARs resulting from volume changes and tissue deformation in oropharyngeal cancer radiotherapy. Treatment review with guidance of a SPC tool may enable objectively and consistently identify significantly deviated fractions

Purpose: This study was to investigate the setup accuracy for automatic rotational corrections using 6 degree of freedom (6DoF) couch and online cone beam computerized tomography (CBCT).
Method(s): A commercial phantom (BAT phantom) with tissue and air equivalent materials was scanned with CT Sim at 1.25 mm plane spacing and 0.98 mm pixel size. A 3D plan was generated in Eclipse for the spherical target of 3 cm diameter located at the center of the phantom. Several lowdensity structures were also outlined as organ at risks (OARs) surrounding the target. The phantom was aligned to the treatment position on the 6DoF couch of a Varian TrueBeam with CBCTverification for both target and OARs outlined before varied rotational errors were introduced in pitch and roll using a titled supporting platform and verified by a calibrated digital level. Following CBCT imaging, the setup corrections were calculated online using the 3D-to-3D auto-matching function on Truebeam and compared against the actual rotational error. We analyzed the deviations at different levels of error.
Result(s): The auto-matching on TrueBeam appeared of good quality even for low contrast and small structures. Deviations of the rotational corrections calculated with 6DoF from the measured are summarized in Tables I-III. The max difference in rotation is 0.7degree for both pitch and roll. However, it also has been observed that there were deviations in every degree of both translational and rotational freedom, which may lead to over-correction in clinic
Conclusion(s): 6 DoF couch and auto-matching offers the convenience for automatic corrections of patient setup in conjunction with CBCT imaging. This preliminary study using a phantom revealed the uncertainties of rotational correction by 6DoF without a deformation of the image. Further study is warranted to establish the criteria for the clinical applications of the auto correction with 6DoF and for the necessary physics QA